Comparing the efficacy of regorafenib and 5-fluorouracil-based rechallenge chemotherapy in the third-line treatment of metastatic colorectal cancer.

BACKGROUND: The optimal treatment for metastatic colorectal cancer (mCRC) after the second line is still controversial. Regorafenib has been the standard of care in this setting as it improved overall survival (OS) compared to placebo. In real-world practice chemotherapy rechallenge is also a preferred option even though supporting evidence is not enough. We aim to compare the efficacy of regorafenib and 5-fluorouracil-based (5-FU) rechallenge treatment in the third line setting of mCRC. METHODS: In this retrospective multi-institutional trial, mCRC patients from 21 oncology centers who progressed after 2 lines of chemotherapy were analyzed. Patients who were treated with regorafenib or rechallenge therapy in the third-line setting were eligible. Rechallenge chemotherapy was identified as the re-use of the 5-FU based regimen which was administered in one of the previous treatment lines. OS, disease control rate (DCR), progression free survival (PFS) and toxicity were analyzed. RESULTS: Three hundred ninety-four mCRC patients were included in the study. 128 (32.5%) were in the rechallenge, and 266 (67.5%) were in the regorafenib group. Median PFS was 5.82 months in rechallenge and 4 months in regorafenib arms (hazard ratio:1.45,95% CI, p = 0.167). DCR was higher in the rechallenge group than regorafenib (77% vs 49.5%, respectively, p = < 0.001). Median OS after the third-line treatment was 11.99 (95% CI, 9.49-14.49) and 8.08 months (95% CI, 6.88-9.29) for rechallenge and regorafenib groups, respectively (hazard ratio:1.51, 95% CI, p < 0.001). More adverse effects and discontinuation were seen with regorafenib treatment. CONCLUSION: Our study revealed that higher disease control and OS rates were achieved with rechallenge treatment compared to regorafenib, especially in patients who achieved disease control in one of the first two lines of therapy.

Real-world outcomes of third-line immune checkpoint inhibitors versus irinotecan-based chemotherapy in patients with advanced gastric cancer: a Korean, multicenter study (KCSG ST22-06).

BACKGROUND: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. METHODS: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). RESULTS: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy. CONCLUSIONS: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).

Chemotherapy re-use versus anti-angiogenic monotherapy as the third-line treatment of patients with metastatic colorectal cancer: a real-world cohort study.

BACKGROUND: There are various recommendations for third-line treatment in mCRC, however, there is no consensus on who is more suitable for particular strategy. Chemotherapy re-use in third-line setting is a common option in clinical practice. This study aimed to investigate the efficacy of third-line chemotherapy re-use by the comparison with that of anti-angiogenic monotherapy, and further find the population more suitable for third-line chemotherapy. METHODS: Using electronic medical records of patients with mCRC, a retrospective cohort study was conducted. A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting as control group were retrospectively collected. Baseline characteristics were analyzed using the χ² test or the Fisher's exact test. ROC curve and surv_cutpoint function of 'survminer' package in R software were used to calculate the cut-off value. Survival curves were plotted with the Kaplan-Meier method and were compared using the log-rank test. The Cox proportional hazard regression model was used to analyze the potential risk factors. RESULTS: A total of 143 patients receiving chemotherapy and 40 patients receiving anti-angiogenic monotherapy in third-line setting were retrospectively collected. Chemotherapy rechallenge was recorded in 93 patients (93/143, 65.0%), and the remaining patients chose new chemotherapeutic drugs that had not been previously used, including irinotecan-based (22/50), oxaliplatin-based (9/50), raltitrexed (9/50), gemcitabine (5/50) and other agents (5/50). The ORR and DCR of third-line chemotherapy reached 8.8%, 61.3%, respectively (anti-angiogenic monotherapy group: ORR 2.6%, DCR 47.4%). The mPFS and mOS of patients receiving chemotherapy were 4.9 and 12.0 m, respectively (anti-angiogenic monotherapy group: mPFS 2.7 m, mOS 5.2 m). Subgroup analyses found that patients with RAS/RAF mutation, longer PFS (greater than 10.6 m) in front-line treatment or larger tumor burden had better prognosis with third-line chemotherapy rather than anti-angiogenic monotherapy. CONCLUSIONS: Third-line chemotherapy re-use was effective in mCRC. Those with more aggressive characteristics (RAS/RAF mutant, larger tumor burden) or better efficacy of previous chemotherapy (longer PFS) were more appropriate for third-line chemotherapy, rather than anti-angiogenic monotherapy.

Real-world treatment patterns in patients initiating third-line therapy for relapsed or refractory multiple myeloma in Germany, Italy, the United Kingdom, France, and Spain.

OBJECTIVES: To retrospectively analyze real-world treatment patterns in patients with relapsed/refractory multiple myeloma (RRMM) who initiated third-line treatment in Europe. METHODS: German and Italian administrative claims data were sourced from the German AOK PLUS health insurance fund and Italian local health units (2016-2020). Data for the United Kingdom (UK), France, and Spain were sourced from medical chart reviews (MCRs) from 2016 to 2018 (historical) and 2019 to 2021 (new) using electronic case report forms. RESULTS: Across all countries, immunomodulatory imide drug (IMiD)-based regimens were prominent in the third-line setting. From 2016 to 2020, lenalidomide-dexamethasone was most common in Italy (18.0%) and Germany (12.7%). From 2019 to 2021, the most common regimen was ixazomib-lenalidomide-dexamethasone (67.5%) in the UK, pomalidomide-dexamethasone (17.1%) in France, and daratumumab-bortezomib-dexamethasone (15.0%) in Spain. In the historical data (2016-2018), third-line lenalidomide- and pomalidomide-dexamethasone doublet use across the UK (>47%), France (>46%), and Spain (>33%) was high. From historical to new, triplet use increased in Spain (>19% to >60%) as did anti-CD38 agent use in France (15.1% to 51.9%) and Spain (19.7% to 42.1%). CONCLUSIONS: From 2016 to 2021, third-line regimens were mostly IMiD based. The MCR data demonstrated evolving treatment choices from 2016 to 2018 and 2019 to 2021, providing insights into uptake of novel agents and current RRMM European clinical practice.

Virologic suppression rate and associated factors for third-line HIV treatment in Addis Ababa, Ethiopia.

BACKGROUND: HIV/AIDS has left a profound impact, leading to significant mortality, morbidity, economic strain, and disability on a global scale. The introduction of antiretroviral therapy (ART) has played a pivotal role in mitigating the economic burden of HIV and enhancing overall productivity. However, the emergence of virological failure presents a critical contemporary challenge within global health, reflecting the complexity of effectively managing HIV treatment outcomes in the 21st century. METHODS: An institutional based, cross-sectional study was conducted. Data were collected using a pretested, structured checklist. Data were edited and cleaned using Microsoft Excel 2016 and analyzed using SPSS version 25. Baseline demographic and clinical data were summarized using descriptive statistics. Multiple logistic regression analysis was run to identify association between dependent and independent variables, by computing odds ratio and 95% confidence interval. A p-value < 0.05 was considered significant. RESULTS: The study delved into the health profile of 117 individuals who were receiving treatment with a third-line antiretroviral therapy (ART) regimen. The findings revealed that the median age of the participants stood at 44 (IQR = ± 17) years and male accounted 53%. The median duration of after HIV diagnosis was found to be 14.25 (± IQR = 5.71) years. Overall virological suppression after third line ART was 76.9% at 6 months. Following adjustment with multiple variable logistic regression, good adherence to medication showed statistical significance in achieving virologic suppression (AOR = 8.48(95% CI: 2.3-30.8), p = 0.001). In contrast, the absence of a change in the second line regimen (AOR = 3.0(95% CI: 0.36-24.8), p = 0.31) and receiving second-line medication for less than three years (AOR = 1.07(95% CI: 0.39-2.95), p = 0.89), and baseline viral load above 100,000 (AOR = 1.74(0.64-2.95), p = 0.27) shows statistically non-significant association with virologic suppression. CLINICAL TRIAL NUMBER: Not applicable. CONCLUSION: This multicenter study provides strong evidence on virological suppression following the use of third-line antiretroviral therapy drugs in Ethiopia. The results of the study indicate rate of Virological suppression after starting third-line ART drugs is significantly linked to good adherence.

Shifts in patient preference of third-line overactive bladder therapy after introduction of the implantable tibial nerve stimulator.

INTRODUCTION: Third-line therapies for overactive bladder (OAB) that are currently recommended include intravesical Onabotulinumtoxin-A injections (BTX-A), percutaneous tibial nerve stimulation (PTNS), and sacral neuromodulation (SNM). The implantable tibial nerve stimulator (ITNS) is a novel therapy that is now available to patients with OAB. OBJECTIVE: The objective of this study was to analyze shifts in patient preference of third-line therapies for OAB after introducing ITNS as an option among the previously established therapies for non-neurogenic OAB. METHODS: A survey was designed and distributed via SurveyMonkey to the platform's audience of U.S. adults of age 18 and older. Screening questions were asked to include only subjects who reported symptoms of OAB. Descriptions of current AUA/SUFU guideline-approved third-line therapies (BTX-A, PTNS, and SNM) were provided, and participants were asked to rank these therapies in order of preference (stage A). Subsequently, ITNS was introduced with a description, and participants were then asked to rank their preferences amongst current guideline-approved therapies and ITNS (stage B). Absolute and relative changes in therapy preferences between stage A and stage B were calculated. Associations between ultimate therapy choice in stage B and participant characteristics were analyzed. RESULTS: A total of 485 participants completed the survey (62.5% female). The mean age was 49.1 ± 36.5 years (SD). The most common OAB symptoms reported were urgency urinary incontinence (UUI) (73.0%) and urinary urgency (68.0%). 29.2% of patients had tried medication for OAB in the past, and 8.0%-10.3% of patients were previously treated with a third-line therapy for OAB. In stage A, participants ranked their first choice of third-line therapy as follows: 28% BTX-A, 27% PTNS, and 13.8% SNM. 26.6% of participants chose no therapy, and 4.5% chose all three equally. In stage B, participants ranked their first choice as follows: 27.6% BTX-A, 19.2% PTNS, 7.8% SNM, and 19.2% ITNS. 21.9% of participants chose no therapy and 4.3% chose all four equally as their first choice. There were both absolute and relative declines in proportions of patients interested in BTX-A, SNM, and PTNS as their first choice of third-line therapy with the introduction of ITNS. Patients originally interested in PTNS in stage A had the greatest absolute change after the introduction of ITNS with 7.8% of participants opting for ITNS in stage B. Those interested in SNM in stage A had the largest relative change in interest, with 43.5% of those originally interested in SNM opting for ITNS in stage B. Finally, with the introduction of ITNS, the number of participants initially not interested in any third-line therapy declined by an absolute change of 4.7% and relative change of 17.6%. Participants experiencing concurrent stress urinary incontinence (SUI) symptoms were more likely to choose a current guideline-approved third-line therapy than ITNS or no therapy at all (p = 0.047). Those who had prior experience with third-line therapies were more likely to choose a third-line therapy other than ITNS as their ultimate choice of therapy in stage B. Of those who had chosen a guideline-approved third-line therapy in stage B (not ITNS), 13.6% had prior experience with BTX-A, 14.7% with PTNS, and 32 (11.2%) with SNM (p < 0.001, p < 0.001, p = 0.009, respectively). CONCLUSION: From our study, it appears that ITNS may attract a subset of patients who would not have otherwise pursued current guideline-approved third-line therapies for OAB. When patients are provided with descriptions of third-line OAB therapies including ITNS as an option, ITNS appears to compete with SNM and PTNS. It is possible that ITNS will provide patients with a different phenotype of neuromodulation therapy that can appeal to a niche OAB population. Given that ITNS devices have been introduced relatively recently to the market, their application will largely depend on cost and payer coverage, provider bias, and patient comorbidities. Further study is needed to understand how these factors interact with and influence patient preference of advanced OAB therapy to understand which patients will most benefit from this treatment modality.

Percutaneous tibial neuromodulation initial therapy compliance and subsequent third-line treatment patterns.

PURPOSE: Percutaneous Tibial Neuromodulation (PTNM) is used to treat Overactive Bladder (OAB). This analysis summarizes patient adherence to PTNM treatment and examines trends of other third-line therapy use during and after PTNM. METHODS: Optum's deidentified Clinformatics® Data Mart Database (CDM) and CMS Research Identifiable Files were queried for adults with OAB symptoms and who underwent PTNM treatment (2019-2020). We evaluated the proportion of patients who completed 12 visits within 1 year, and defined patients as treatment compliant if 12 PTNM visits were completed within 12 weeks. We then identified the proportion of patients who used other third-line therapies after PTNM and stratified these patients based on their PTNM therapy compliance status. RESULTS: 2302 patients met selection criteria from CDM and 16,473 patients from CMS. The proportion of patients completing a full PTNM treatment course increased over time; from 16% at week 12% to 42% by week 52 (CDM) and 24% to 38% (CMS). Other third-line therapy use increased over time and was higher for PTNM noncompliant versus compliant patients at 52 weeks: onabotulinumtoxinA was 6.5% versus 5.7% for noncompliant versus compliant (CMS, p = 0.0661) and 6.4% versus 4.9% (CDM, p = 0.035), SNM trial procedure was 6.5% versus 2.5% (CDM, p = 0.002) and 4.2% versus 2.0% (CMS, p = 0.010). CONCLUSIONS: Most patients are noncompliant with recommended PTNM treatment regimen. Albeit low, third-line therapy was pursued more frequently by noncompliant patients. Given low compliance, the effectiveness of PTNM may be compromised. Alternative implantable technologies may be needed to assure effectiveness of neuromodulation.

Fluid intake behavior in women with refractory overactive bladder undergoing third line therapy.

INTRODUCTION AND OBJECTIVES: Fluid intake has been shown to be related to urinary symptoms, but no studies to date have investigated the effect of fluid intake on urinary symptoms in women with refractory overactive bladder (OAB). As this group of women are considered to have a possible unique pathophysiologic mechanism of OAB, we investigated the relationship between fluid intake, fluid intake behavior, and urinary symptoms in women with refractory OAB. METHODS: A prospective cross-sectional study of women with refractory OAB was conducted by assessing the relationship between fluid intake and lower urinary tract symptoms (LUTS) in women undergoing third line OAB therapies. Fluid intake and behavior were measured by the questionnaire based voiding diary and urinary symptoms were measured by the International Consultation on Incontinence Questionnaire for Female Lower Urinary Tract Symptoms (ICIQ-FLUTS). The relationship between fluid intake and symptom severity was assessed using Spearman's rank correlation and χ2  tests. RESULTS: Of the 126 individuals undergoing third line therapy for OAB, 60 (48%) underwent intradetrusor onabotulinumtoxinA injection (BTX) injection, 42 (33%) peripheral tibial nerve stimulation, and 24 (19%) sacral neuromodulation. The mean total daily fluid intake was 2567.0 ± SD 1292.4 mL and did not differ significantly across treatment groups. Total fluid intake was weakly correlated with worse filling-type LUTS (r = 0.241, p = 0.007), and there was no relationship between LUTS and caffeinated fluid intake. Half (52%) of the subjects reported current fluid restricting behavior to control urinary symptoms, but this behavior was not correlated with LUTS severity (all p > 0.05). Patients that currently use tobacco have greater LUTS (current = 25.8 ± SD 9.5, former = 14.8 ± SD 6.1, never = 15.0 ± SD 6.1; p < 0.001). BMI was also positively correlated with worse incontinence symptoms (r = 0.351, p < 0.001). CONCLUSIONS: Fluid intake along with other lifestyle factors, including tobacco use and weight, are minimally related to the symptomatology seen in women with refractory OAB. Further studies are needed to assess if behaviors change during treatment with third line therapies, and if these behavioral changes may affect treatment response.

Sacral neuromodulation in nursing home residents: Predictors of success and complications in a national cohort of older adults.

AIMS: There is limited evidence to support the efficacy of sacral neuromodulation (SNM) for older adults with overactive bladder (OAB). This study aims to report outcomes following SNM among nursing home (NH) residents, a vulnerable population with high rates of frailty and comorbidity. METHODS: This is a retrospective cohort study of long-stay NH residents who underwent a trial of percutaneous nerve evaluation (PNE) or Stage 1 permanent lead placement (Stage 1) between 2014 and 2016. Residents were identified using the Minimum Data Set linked to Medicare claims. The primary outcome of this study was successful progression from trial to implant. Rates of 1-year device explant/revisions were also investigated. RESULTS: Trial of SNM was observed in 1089 residents (mean age: 77.9 years). PNE was performed in 66.9% of residents and 33.2% underwent Stage 1. Of Stage 1 procedures, 23.8% were performed with simultaneous device implant (single-stage). Overall, 53.1% of PNEs and 72.4% of Stage 1 progressed to device implant, which was associated with Stage 1 procedure versus PNE (adjusted relative risk [aRR]: 1.34; 95% confidence interval [95% CI]: 1.21-1.49) and female versus male sex (aRR: 1.26; 95% CI: 1.09-1.46). One-year explant/revision was observed in 9.3% of residents (6.3% for PNE, 10.5% for Stage 1, 20.3% single-stage). Single stage procedure versus PNE was significantly associated with device explant/revision (aRR: 3.4; 95% CI: 1.9-6.2). CONCLUSIONS: In this large cohort of NH residents, outcomes following SNM were similar to previous reports of younger healthier cohorts. Surgeons managing older patients with OAB should use caution when selecting patients for single stage SNM procedures.

Virological outcomes of third-line antiretroviral therapy in a global context: a systematic reviews and meta-analysis.

BACKGROUND: Despite remarkable progress, HIV's influence on global health remains firm, demanding continued attention. Understanding the effectiveness of third-line antiretroviral therapy in individuals who do not respond to second-line drugs is crucial for improving treatment strategies. The virological outcomes of third-line antiretroviral therapy vary from study to study, highlighting the need for robust global estimates. METHODS: A comprehensive search of databases including PubMed, MEDLINE, International Scientific Indexing, Web of Science, and Google Scholar, was conducted. STATA version 17 statistical software was used for analysis. A random-effects model was applied to compute the pooled estimates. Subgroup analysis, heterogeneity, publication bias, and sensitivity analysis were also performed. The prediction interval is computed to estimate the interval in which a future study will fall. The GRADE tool was also used to determine the quality of the evidence. RESULTS: In this systematic review and meta-analysis, 15 studies involving 1768 HIV patients receiving third-line antiretroviral therapy were included. The pooled viral suppression of third-line antiretroviral therapy was 76.6% (95% CI: 71.5- 81.7%). The viral suppression rates at 6 and 12 months were 75.5% and 78.6%, respectively. Furthermore, third-line therapy effectively suppressed viral RNA copy numbers to ≤ 50 copies/mL, ≤ 200 copies/mL, and ≤ 400 copies/mL with rates of 70.7%, 85.4%, and 85.7%, respectively. CONCLUSION: More than three-fourths of patients on third-line antiretroviral therapy achieve viral suppression. Consequently, improving access to and timely initiation of third-line therapy may positively impact the quality of life for those with second-line treatment failure.

Estimated cost of VEGFR TKI associated adverse events in metastatic renal cell carcinoma patients.

INTRODUCTION: The majority of metastatic renal cell carcinoma (mRCC) patients receive one or more VEGFR TKI agents, alone or in combination with an immune-oncology (IO) agent or an mTOR inhibitor. To date, the cost of adverse events (AEs) common to VEGFR TKIs has not been quantified. This study estimated the potential impact of differences in VEGFR TKI AE profiles on treatment cost efficiency in the relapsed/refractory (R/R) setting. METHODS: Patients with documented mRCC who were treated with VEGFR TKI therapies between Jan 2015 and Mar 2021 were identified using EMR. ICD-10 diagnosis codes were used to identify the first occurrence of each class effect AE. Patients were matched to 3rd party insurance claims, and costs associated to TKI AEs within 90 days of index event were captured. Average per patient AE cost data was calculated and applied to published incidence data to estimate regimen-specific AE total cost burden within a hypothetical commercial plan for mRCC patients undergoing treatment in the R/R setting. RESULTS: The highest total cost for AE management was attributed to lenvatinib and everolimus use at $13,303, followed closely by sunitinib at $13,092. Tivozanib treatment was associated with the lowest total cost of AE management at $7,523, driven by the relatively lower incidence of certain high-cost AEs. CONCLUSIONS: The estimated costs of managing VEGFR TKI class-effect AEs were lowest with tivozanib, and highest with lenvatinib and everolimus, indicating potentially differential healthcare resource burden by TKI regimen. The use of tivozanib in the 3 L + mRCC setting suggests potential costs offsets when compared to other TKI regimens.

FOLFOX regimen after failure of fluorouracil and leucovorin plus nanoliposomal-irinotecan therapy for advanced pancreatic cancer: a retrospective observational study.

BACKGROUND: Fluorouracil, leucovorin (5FU/LV), and nanoliposomal-irinotecan (nal-IRI) combination therapy has been established as the second-line treatment for advanced pancreatic ductal adenocarcinoma. Oxaliplatin with 5FU/LV (FOLFOX) is often used as a subsequent treatment, although its efficacy and safety are yet to be fully elucidated. We aimed to evaluate the efficacy and safety of FOLFOX as a third- or later-line treatment for patients with advanced pancreatic ductal adenocarcinoma. METHODS: We conducted a single-centre, retrospective study that enrolled 43 patients who received FOLFOX after failure of gemcitabine-based regimen followed by 5FU/LV + nal-IRI therapy between October 2020 and January 2022. FOLFOX therapy consisted of oxaliplatin (85 mg/m2), levo-leucovorin calcium (200 mg/m2) and 5-FU (2400 mg/m2) every 2 weeks per cycle. Overall survival, progression-free survival, objective response, and adverse events were evaluated. RESULTS: At the median follow-up time of 3.9 months in all patients, the median overall survival and progression-free survival were 3.9 months (95% confidence interval [CI], 3.1-4.8) and 1.3 months (95% CI, 1.0-1.5), respectively. Response and disease control rates were 0 and 25.6%, respectively. The most common adverse event was anaemia in all grades followed by anorexia; the incidence of anorexia and grades 3 and 4 was 21 and 4.7%, respectively. Notably, grades 3-4 peripheral sensory neuropathy was not observed. Multivariable analysis revealed that a C-reactive protein (CRP) level of > 1.0 mg/dL was a poor prognostic factor for both progression-free survival and overall survival: hazard ratios were 2.037 (95% CI, 1.010-4.107; p = 0.047) and 2.471 (95% CI, 1.063-5.745; p = 0.036), respectively. CONCLUSION: FOLFOX as a subsequent treatment after failure of second-line treatment with 5FU/LV + nal-IRI is tolerable, although its efficacy is limited, particularly in patients with high CRP levels.

Determining patient preferences in the treatment of medication-refractory overactive bladder.

INTRODUCTION: Overactive bladder (OAB) is often suboptimally addressed by behavioral or pharmacological treatments. Less than 15% of patients choose to pursue advanced OAB therapy (sacral nerve stimulation [SNS], percutaneous tibial nerve stimulation [PTNS], and bladder onabotulinum toxin type-A [BTX-A]). We seek to better understand which factors are most important to patients when choosing a third-line therapy. METHODS/MATERIALS: We developed a conjoint analysis survey that included five attributes of the third-line options for OAB (SNS, PTNS, and BTX-A). We administered the survey to new patients with urinary incontinence at two institutions. A hierarchical Bayes random effects regression analysis was used to determine the relative importance of the attributes. A choice simulator was used to model which third-line treatment options patients preferred. We followed patients to see if they pursued their predicted treatment. RESULTS: A total of 108 patients completed the study of whom 89% were women. There was representation from all age groups. The most important attributes of decision-making were the frequency of future procedures, the risk of catheterization, and the need for a device. On market simulation, SNS was the preferred treatment option (47%), followed by PTNS (29%) and BTX-A (14%). Only 10% of patients did not find any treatment option acceptable. CONCLUSIONS: Frequent follow-up, risk of catheterization, and the need for a device were the most important attributes when making a decision on third-line OAB therapy. On market simulation, SNS is the preferred treatment for all age groups though the ultimate choice in third-line therapy may be affected by external factors.

Efficacy and Safety of Third-Line Apatinib plus Chemotherapy in Metastatic Triple-Negative Breast Cancer Patients: A Multicenter, Retrospective, Cohort Study.

Apatinib is a tyrosine kinase inhibitor (TKI) that targets vascular endothelial growth factor receptor 2 (VEGFR2) as an effective anti-angiogenic agent. The current study intended to explore the treatment efficacy and safety profile of third-line apatinib plus chemotherapy in metastatic triple-negative breast cancer (mTNBC) patients. This multicenter, retrospective, cohort study analyzed 97 mTNBC patients who underwent third-line apatinib plus single-agent chemotherapy (N = 45) or single-agent chemotherapy (N = 52). The objective response rate (44.4% vs. 19.2%, P = 0.007) and disease control rate (77.8% vs. 48.1%, P = 0.003) were higher in the apatinib plus chemotherapy group than in the chemotherapy group. The apatinib plus chemotherapy group had a longer median progression-free survival (PFS) [6.9 (95% confidence interval, CI: 5.2-8.6) vs. 4.3 (95%CI: 3.2-5.4) months, P = 0.008] and overall survival (OS) [11.6 (95% CI: 9.3-13.9) vs. 9.0 (95% CI: 7.3-10.7) months, P = 0.012] than the chemotherapy group. Further adjustment of multivariate Cox's regression analysis verified that apatinib plus chemotherapy (vs. chemotherapy) resulted in a longer PFS (P = 0.003) and OS (P = 0.010). There was no difference in adverse events between the two groups, except that the incidence of hypertension was higher in the apatinib plus chemotherapy group than in the chemotherapy group (P = 0.018); meanwhile, the grade 3-4 adverse events in the apatinib plus chemotherapy group included hypertension (13.3%), neutropenia (8.9%), nausea and vomiting (4.4%), fatigue (4.4%), leukopenia (4.4%), thrombocytopenia (2.2%), and hand-foot syndrome (2.2%). Third-line apatinib plus chemotherapy may achieve a more satisfying survival benefit and no obvious safety concerns in mTNBC patients compared with mono-chemotherapy. However, more large-scale, randomized studies are warranted for further validation.

[The efficacy of chemotherapy re-challenge in third-line setting for metastatic colorectal cancer patients: a real-world study].

Objective: To explore the efficacy of chemotherapy re-challenge in the third-line setting for patients with metastatic colorectal cancer (mCRC) in the real world. Methods: The clinicopathological data, treatment information, recent treatment efficacy, adverse events and survival data of mCRC patients who had disease progression after treatment with oxaliplatin-based and/or irinotecan-based chemotherapy and received third-line chemotherapy re-challenge from January 2013 to December 2020 at Tianjin Medical University Cancer Institute and Hospital were retrospectively collected. Survival curves were plotted with the Kaplan-Meier method, and the Cox proportional hazard model was used to analyze the prognostic factors. Results: A total of 95 mCRC patients were included. Among them, 32 patients (33.7%) received chemotherapy alone and 63 patients (66.3%) received chemotherapy combined with targeted drugs. Eighty-three patients were treated with dual-drug chemotherapy (87.4%), including oxaliplatin re-challenge in 35 patients and irinotecan re-challenge in 48 patients. The remaining 12 patients were treated with triplet chemotherapy regimens (12.6%). Among them, as 5 patients had sequential application of oxaliplatin and irinotecan in front-line treatments, their third-line therapy re-challenged both oxaliplatin and irinotecan; 7 patients only had oxaliplatin prescription before, and these patients re-challenged oxaliplatin in the third-line treatment. The overall response rate (ORR) and disease control rate (DCR) reached 8.6% (8/93) and 61.3% (57/93), respectively. The median progression free survival (mPFS) and median overall survival (mOS) were 4.9 months and 13.0 months, respectively. The most common adverse events were leukopenia (34.7%) and neutropenia (34.7%), followed by gastrointestinal adverse reactions such as nausea (32.6%) and vomiting (31.6%). Grade 3-4 adverse events were mostly hematological toxicity. Cox multivariate analysis showed that gender (HR=1.609, 95% CI: 1.016-2.548) and the PFS of front-line treatments (HR=0.598, 95% CI: 0.378-0.947) were independent prognostic factors. Conclusion: The results suggested that it is safe and effective for mCRC patients to choose third-line chemotherapy re-challenge, especially for patients with a PFS of more than one year in front-line treatments.

ALK Inhibitors or Chemotherapy for Third Line in ALK-positive NSCLC? Real-world Data.

OBJECTIVES: ALK inhibitors (ALKi) are the standard-of-care treatment for metastatic ALK-rearranged non-small cell lung cancer (NSCLC) in the first- and second-line setting. We conducted a real-world multi-institutional analysis, aiming to compare the efficacy of third-line ALKi versus chemotherapy in these patients. METHODS: Consecutive ALK-positive metastatic NSCLC patients treated with at least one ALKi were identified in the working databases of 7 Israeli oncology centers (the full cohort). Demographic and clinical data were collected. Patients receiving any systemic treatment beyond 2 ALKi comprised the third-line cohort, whether a third ALKi (group A) or chemotherapy (group B). Groups A and B were compared in terms of overall survival (OS) and time-to-next-treatment line (TNT). RESULTS: At a median follow-up of 41 months (95% confidence interval [CI]: 32-55), 80 (47.1%) have died. Median OS (mOS) in the full cohort (n = 170) was 52 months (95% CI: 32-65). Number of ALKi (hazard ratio [HR] 0.765; 95% CI: 0.61-0.95; P = .024) and age (HR 1.02, 95% CI: 1.01-1.04, P = .009) significantly associated with OS in the full cohort. The third-line cohort included 40 patients, of which 27 were treated with third ALKi (group A) and 13 treated with chemotherapy (group B). mOS from third-line initiation was 27 months in group A (95% CI: 13-NR) and 13 months for group B (95% CI: 3-NR); the difference was not significant (NS; P = .12). Chemotherapy as first line (HR 0.17, 95% CI: 0.05-0.52, P = .002) and a higher number of ALKi (HR 0.38, 95% CI: 0.20-0.86, P = .011) associated significantly with longer OS of the third-line cohort. TNT was 10 months for group A (95% CI: 5-19) and 3 months for group B (95% CI: 0-NR); the difference was NS (P = .079). CONCLUSION: We report mature real-world data of more than 4-year mOS in ALK-positive patients. The number of ALKi given was associated with a better outcome. OS and TNT demonstrated a statistically nonsignificant trend for a better outcome in patients receiving a third-line ALKi.

Oral phenazopyridine vs intravesical lidocaine for bladder onabotulinumtoxinA analgesia: a randomized controlled trial.

BACKGROUND: The efficacy of intradetrusor onabotulinumtoxinA injections for the management of idiopathic overactive bladder has been well-established. The injections are typically performed in the office setting using local analgesia, most commonly a 20 to 30-minute intravesical instillation of lidocaine. There are limited data evaluating alternative bladder analgesics. OBJECTIVE: To compare pain scores with preprocedure oral phenazopyridine vs intravesical lidocaine in women undergoing intradetrusor onabotulinumtoxinA injections for idiopathic overactive bladder. STUDY DESIGN: Nonpregnant adult females with idiopathic overactive bladder, scheduled for office injection of 100 units of intradetrusor onabotulinumtoxinA were randomized to either 200 mg of oral phenazopyridine taken 1 to 2 hours preprocedure or a 20-minute preprocedure intravesical instillation of 50 mL of 2% lidocaine. We excluded participants with neurogenic bladders, and those who had received intradetrusor onabotulinumtoxinA injections in the previous 12 months. The primary outcome was pain measured by a 100-mm visual analog scale. Demographic characteristics and overall satisfaction with the procedure were also recorded. Providers answered questions about cystoscopic visualization, ease of procedure, and perception of participant comfort. Prespecified noninferiority margin was set to equal the anticipated minimum clinically important difference of 14 mm. A planned sample of 100 participants, 50 in each treatment arm, provided 80% power to detect noninferiority at a significance level of.05. We performed a modified intention-to-treat analysis and compared variables with the t test or the Fisher exact test. RESULTS: A total of 111 participants were enrolled, and complete data were obtained for 100 participants; 47 participants were randomized to phenazopyridine and 53 to lidocaine. Baseline characteristics did not differ between groups. There were 19.6% and 20.8% of participants in the phenazopyridine and lidocaine groups, respectively, who previously underwent intradetrusor onabotulinumtoxinA injections. The mean postprocedure pain was 2.7 mm lower in the phenazopyridine group than in the lidocaine group (95% confidence interval, -11.3 to 10.7), demonstrating noninferiority. More than 90% of participants in both groups stated that the pain was tolerable. Slightly more participants reported being "very satisfied" in the lidocaine group, although this was not statistically significant (50.0% vs 40.4%; P=.34). Providers reported clear visualization in 89.4% of participants in the phenazopyridine group and in 100% of participants in the lidocaine group (P=.02). Provider perception of participant comfort and overall ease of procedure were not different between groups. Length of time in the exam room was significantly shorter in the phenazopyridine than in the lidocaine group (44.4 vs 57.5 minutes; P=.0003). CONCLUSION: In women receiving intradetrusor onabotulinumtoxinA injections for idiopathic overactive bladder, oral phenazopyridine was noninferior to intravesical lidocaine for procedural pain control. Phenazopyridine is well-tolerated by participants, allows for the procedure to be performed with similar ease, and is associated with shorter appointment times.

An analysis of factors that influence patient preference of third-line therapy for overactive bladder.

OBJECTIVE: Patients with overactive bladder (OAB) refractory to first- and second-line therapy may pursue third-line therapies, including intradetrusor onabotulinum toxin-A (BTX), peripheral tibial nerve stimulation (PTNS), and sacral neuromodulation (SNM). The factors that influence patient preference for each treatment modality have not yet been explored. This study sought to investigate the specific parameters that patients consider in choosing a third-line therapy for OAB. METHODS: Patients refractory to first- and second-line therapies for OAB were identified in our outpatient clinic and asked to watch an educational video providing information on the risks and benefits of each third-line treatment option. They were then given a questionnaire to rank their preference of therapy and select reasons for why they found each therapy favorable and unfavorable. Patients under age 18 years, non-English speakers, those with a developmental disability, and those with a diagnosis of neurogenic bladder were excluded. RESULTS: Of the 98 patients included in the study, 40 participants (40.8%) chose intradetrusor BTX injections, 34 (34.7%) chose PTNS, and 16 (16.3%) chose SNM as their first choice. Seven patients (7.1%) chose none of the offered therapies, and one patient (1.0%) chose all three therapies with equal preference. BTX was found most attractive for its long efficacy (47%); its least attractive feature was the potential need for self-catheterization due to urinary retention (54%). PTNS was found most attractive for being a nonsurgical option (32%) and having no reported significant complications (39%); its least attractive feature was need for frequent office visits (61%). SNM was found most attractive for its potential for long-term relief without frequent office visits (53%); its least attractive feature was need for an implanted device (33%). Patients opting for SNM had higher scores on Urinary Distress Inventory-6 and Incontinence Impact Questionnaire-7 questionnaires when compared to patients opting for BTX injections or PTNS (p < 0.05). 47.4% of patients eventually pursued a third-line therapy. Of those, there was a 67.6% concordance rate between the therapy patients ranked first and the therapy they eventually underwent. CONCLUSIONS: Patients with more severe OAB symptoms opt for more invasive and less time-consuming therapy with the potential for long-term relief, namely SNM. Despite thorough counseling, many patients do not progress to advanced OAB therapies. Understanding factors that influence patients' affinity toward a specific type of treatment can aid with individualized counseling on third-line OAB therapies.

Barriers and facilitators to overactive bladder therapy adherence.

AIMS: To provide an overview of the barriers and facilitators to overactive bladder (OAB) therapy initiation and adherence. METHODS: A PubMed and Embase literature search was conducted to identify barriers to OAB therapy adherence. RESULTS: OAB therapy adherence is associated with improvements in urinary symptoms, and quality of life with reductions in annual costs for OAB-related expenditures. However, adherence rates to behavioral therapies are as low as 32% at 1 year, only 15%-40% of treated patients remain on oral medications at 1 year due to several factors (e.g., inadequate efficacy, tolerability, and cost), and 5%-10% of OAB patients progress to advanced therapies. While some common barriers to therapy adherence are often fixed (e.g., costs, lack of efficacy, time, side effects, treatment fatigue), many are modifiable (e.g., lack of knowledge, poor relationships, negative experiences, poor communication with providers). Patient-centered care may help address some modifiable barriers. Emerging data demonstrate that patient-centered care in the form of treatment navigators improves OAB therapy adherence and progression to advanced therapies in the appropriate patient. CONCLUSIONS: There are numerous modifiable barriers to OAB therapy adherence. A patient-centered lens is needed to elicit patient goals, establish realistic treatment expectations, and tailor therapy to improve therapy adherence, optimize outcomes, and reduce healthcare expenditures. Further research is needed to develop and study low-cost, scalable solutions.

Real-world overall survival of patients receiving cetuximab in later lines of treatment for metastatic colorectal cancer.

Aim: To examine characteristics of and treatment duration and real-world overall survival (rwOS) in patients receiving cetuximab as second-line (2L) or third-line (3L) treatment for metastatic colorectal cancer. Materials & methods: This was a retrospective study of 1096 and 684 patients in 2L and 3L cohorts, respectively. Results: The most common cetuximab-based regimens were cetuximab + folinic acid, fluorouracil and irinotecan (2L: 44%; 3L: 32%) and cetuximab + irinotecan (2L: 28%; 3L: 35%). Kaplan-Meier survival estimates and stepwise Cox regression model analysis demonstrated median treatment duration and rwOS of 3.7 and 14.4 months, respectively, in patients receiving treatment in the 2L cohort. In the 3L cohort, treatment duration was 3.3 months and rwOS was 12.0 months. Conclusion: This large real-world study provides evidence of rwOS in patients with metastatic colorectal cancer receiving cetuximab-based regimens as 2L or 3L treatment.

In this retrospective study, the authors examined baseline characteristics of and treatment duration and real-world overall survival (rwOS) in 1096 and 684 patients with metastatic colorectal cancer receiving cetuximab as second-line (2L) and third-line (3L) treatment, respectively. The most common cetuximab-based regimens were cetuximab + folinic acid, fluorouracil and irinotecan (2L: 44%; 3L: 32%) and cetuximab + irinotecan (2L: 28%; 3L: 35%). Median treatment duration and rwOS were 3.7 and 14.4 months, respectively, in patients receiving treatment in the 2L cohort. In the 3L cohort, median treatment duration was 3.3 months and rwOS was 12.0 months. This large real-world study provides evidence of rwOS in patients with metastatic colorectal cancer receiving cetuximab-based regimens as 2L or 3L treatment.